Journal article
Arginase-I enhances vascular endothelial inflammation and senescence through eNOS-uncoupling.
- Zhu C Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland.
- Yu Y Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland.
- Montani JP Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland.
- Ming XF Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland. xiu-fen.ming@unifr.ch.
- Yang Z Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland. zhihong.yang@unifr.ch.
- 2017-02-04
Published in:
- BMC research notes. - 2017
Arginase-I
Endothelial cell
Inflammation
Senescence
eNOS-uncoupling
Acetylcysteine
Adenoviridae
Animals
Arginase
Cell Line, Tumor
Cells, Cultured
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p21
Endothelium, Vascular
Free Radical Scavengers
Genetic Vectors
Human Umbilical Vein Endothelial Cells
Humans
Immunoblotting
Inflammation
Intercellular Adhesion Molecule-1
Mice
Nitric Oxide Synthase Type III
Transfection
Tumor Suppressor Protein p53
Vascular Cell Adhesion Molecule-1
beta-Galactosidase
English
BACKGROUND
Augmented arginase-II (Arg-II) is implicated in endothelial senescence and inflammation through a mutual positive regulatory circuit with S6K1. This study was conducted to investigate whether Arg-I, another isoform of arginase that has been also reported to play a role in vascular endothelial dysfunction, promotes endothelial senescence through similar mechanisms.
RESULTS
The non-senescent human endothelial cells from umbilical veins (passage 2 to 4) were transduced with empty recombinant adenovirus vector (rAd/CMV) as control or rAd/CMV-Arg-I to overexpress Arg-I. Overexpressing Arg-I promoted eNOS-uncoupling, enhanced senescence markers including p53-S15, p21 and senescence-associated β-galactosidase (SA-β-gal) staining, and increased inflammatory vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) as well as monocyte adhesion to endothelial cells without activating S6K1. All the effects of Arg-I were inhibited by the anti-oxidant N-acetylcysteine (NAC).
CONCLUSIONS
Our study demonstrates that Arg-I promotes endothelial senescence and inflammatory responses through eNOS-uncoupling unrelated to activation of the S6K1 pathway.
Augmented arginase-II (Arg-II) is implicated in endothelial senescence and inflammation through a mutual positive regulatory circuit with S6K1. This study was conducted to investigate whether Arg-I, another isoform of arginase that has been also reported to play a role in vascular endothelial dysfunction, promotes endothelial senescence through similar mechanisms.
RESULTS
The non-senescent human endothelial cells from umbilical veins (passage 2 to 4) were transduced with empty recombinant adenovirus vector (rAd/CMV) as control or rAd/CMV-Arg-I to overexpress Arg-I. Overexpressing Arg-I promoted eNOS-uncoupling, enhanced senescence markers including p53-S15, p21 and senescence-associated β-galactosidase (SA-β-gal) staining, and increased inflammatory vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) as well as monocyte adhesion to endothelial cells without activating S6K1. All the effects of Arg-I were inhibited by the anti-oxidant N-acetylcysteine (NAC).
CONCLUSIONS
Our study demonstrates that Arg-I promotes endothelial senescence and inflammatory responses through eNOS-uncoupling unrelated to activation of the S6K1 pathway.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13104-017-2399-x
- PMID 28153047
- Persistent URL
- https://sonar.ch/global/documents/138949
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